Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
  • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
  • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• the present invention relates to 3- ⁇ (2S, 4S) -4- [4- (3-methyl-1-phenol) useful as a dipeptidyl peptidase IV (hereinafter referred to as DPP-IV) inhibitor.
• DPP-IV dipeptidyl peptidase IV
• DPP-IV inhibitors inhibit the inactivity of glucagon-like peptide-1 (hereinafter referred to as GLP-1) in plasma and enhance its incretin action. It is in the research and development stage as a drug that is useful as a drug that can be effective in the treatment of diabetes, particularly type 2 diabetes (see Patent Documents 1 to 6 and Non-Patent Document 1).
• Compound I 3- ⁇ (2 S, 4S) -4- [4- (3-methyl-1-phenol-1H-pyrazole-5- ) Piperazine-1-yl] pyrrolidin-2-ylcarbonyl ⁇ thiazolidine (hereinafter referred to as Compound I).
• Compound I is described in the form of the trihydrochloride salt, but this salt has pharmaceutically undesirable properties in terms of stability and hygroscopicity and is difficult to manufacture in the same form with reproducibility. It was recognized that In order to meet the regulatory requirements in drug development, in particular, certain quality compounds must be produced reproducibly, so these properties found in the trihydrochloride of Compound I are important for drug development. It is considered disadvantageous.
• Patent Document 7 “I Compound I” and other salts of other thiazolidine derivatives are disclosed as example compounds. There has been a discussion about polymorphism.
• crystal polymorphism The ability of a substance to crystallize into two or more crystal structures is known as polymorphism, and individual crystal forms are called crystal polymorphs. Different crystal polymorphs of the same compound may have completely different physical properties such as storage stability and solubility. these Differences in physical properties may lead to differences in action effects. Because of these differences, the study of individual crystal polymorphs and mixtures of crystal polymorphs is particularly useful in drug development.
• Patent Document 1 International Publication No. 97/040832 Pamphlet
• Patent Document 2 Pamphlet of International Publication No. 98/019998
• Patent Document 3 US Pat. No. 5,939,560
• Patent Document 4 International Publication No. 01/055105 Pamphlet
• Patent Document 5 International Publication No. 02/002560 Pamphlet
• Patent Document 6 International Publication No. 02/062764 Pamphlet
• Patent Document 7 International Publication No. 02/014271 Pamphlet
• Non-Patent Document 1 J. Med. Chem., 47 (17), 4135-4141 (2004)
• An object of the present invention is to provide a compound I having excellent characteristics in terms of stability, solubility, hygroscopicity, bioavailability, and the like, and a reproducible crystal structure, which are desired for a pharmaceutical product. And to provide a method for producing them.
• the present inventors prepared one or more tribasic acid salts of Compound I, characterized the crystals of the respective salts or their solvates, and preferred in terms of stability and hygroscopicity. Has ⁇ characteristics A new salt of Compound I was found. As a result of further intensive studies, the inventors have found a stable industrial preparation method for the novel salt of the present invention and have completed the present invention.
• the gist of the present invention resides in the following salts (1) to (33) or a solvate thereof, and a production method thereof.
• Organic or inorganic monobasic acids are hydrochloric acid, hydrobromic acid, nitric acid, mesylic acid, tosylic acid, besylic acid, hydrochloric acid, naphthalene-1-sulfonic acid, naphthalene-2-sulfonic acid, gallic acid, Is camphorsulfonic acid, the salt according to the above (1), or a solvate thereof (however, when the monobasic acid is hydrochloric acid, the salt is 2 or 2.5 hydrochloride),
• Solubility in water at ambient temperature is 7 mg / mL! And 2 g / mL monobasic acid and 3- ⁇ (2S, 4S) -4- [4- (3-methyl-1-phenol -L-1H-pyrazole-5-yl) piperazine-1-yl] pyrrolidine-2-ylcarbol ⁇ thiazolidine salt, or a solvate thereof,
• the diffraction angle represented by 20 has peaks at 5.4 °, 13.4 °, 14.4 °, 22.6 ° and 26.5 ° (each ⁇ 0.2 °). (14) or a hydrate thereof,
• the acceptable solvent is water and / or the solvent selected in the “residual solvent Q3C ICH guidelines” with a daily intake allowance (“PDE”) exceeding 10 mg / day.
• PDE daily intake allowance
• Each of the novel crystalline polymorphs of a salt of Compound I or a solvate thereof has improved stability, improved hygroscopicity (deliquescent), rapid isolation from the solvent, and formulation Has one or more properties selected from the ease of preparation and facilitates the development of Compound I as a pharmaceutical.
• FIG. 1 is a measurement result of powder X-ray diffraction of the title compound of Example 4.
• the Y axis is the diffraction intensity, and the horizontal axis is the diffraction angle (2 ⁇ ).
• FIG. 2 is a measurement result of powder X-ray diffraction of the compound of Example 5 (1).
• the Y axis is the diffraction intensity, and the horizontal axis is the diffraction angle (2 ⁇ ).
• FIG. 3 is a measurement result of powder X-ray diffraction of the compound of Example 5 (2).
• the Y axis is the diffraction intensity, and the horizontal axis is the diffraction angle (2 ⁇ ).
• FIG. 4 is a result of measuring powder X-ray diffraction of the compound of Example 5 (3).
• the Y axis is the diffraction intensity, and the horizontal axis is the diffraction angle (2 ⁇ ).
• FIG. 5 is a measurement result of hygroscopicity of the title compound of Example 3.
• 101 is the adsorption of water to the compound at the horizontal axis humidity
• ⁇ ichi is the water desorption from the compound at the horizontal axis humidity.
• the trihydrochloride of compound I can be produced according to the synthesis method described as Example 222 of WO 02/14271.
• This base uses an appropriate base such as an alkali metal or alkaline earth metal carbonate (sodium bicarbonate, sodium carbonate, or potassium carbonate) or an alkali metal or alkaline earth metal hydroxide. (Such as sodium hydroxide or potassium hydroxide).
• a hydrocarbon solvent such as benzene or toluene
• a halogenated hydrocarbon solvent dimethoxycarbon solvent
• dichloromethane, dichloroethane, chloroform, or Compound I can be obtained by extraction with tetrasalt, carbon, etc.
• ethyl acetate ethyl acetate
• the 2.5 hydrobromide salt of Compound I can also be produced by the following scheme.
• This reductive amination reaction is carried out with respect to 1 mol of the compound represented by the formula (II) or a salt thereof.
• the compound represented by the formula (III) is used in an amount of about 0.5 to 10 mol, preferably about 1 to 2 mol, and a metal hydride complex (sodium borohydride, sodium cyanoborohydride, triacetoxy borohydride).
• a complex hydrogen compound such as sodium or diborane is used in an amount of about 0.5 to 10 moles, preferably about 1 to 2 moles, and an acidic catalyst (acetic acid, P-toluenesulfonic acid, or In an inert solvent in the presence of boron fluoride 'jetyl ether complex, etc.).
• inert solvents examples include alcohols (methanol, ethanol, 1-propanol, 2-propanol (hereinafter referred to as IPA), butanol, etc.), nitriles (acetonitrile, propio-tolyl, etc.), Amides (formamide, ⁇ , ⁇ -dimethylformamide, ⁇ , ⁇ -dimethylacetamide, or 1,3-dimethyl-2-imidazolidinone), ethers (jetyl ether, diisopropyl ether, t- Butyl methyl ether, 1,4-dioxane, or tetrahydrofuran (hereinafter referred to as THF)), halogenated hydrocarbons (such as dichloromethane, chloroform, or 1,2-dichloroethane), hydrocarbons ( n-hexane, cyclohexane, benzene, toluene, etc.), or any mixed solvent thereof.
• alcohols m
• the reaction temperature is -20 to 200 ° C, preferably 0 to 80 ° C, and the reaction time is about 0.5 to 96 hours, preferably 0.5 to 24 hours.
• the reaction temperature is ⁇ 20 to 200 ° C., preferably 0 to 100 ° C., and the reaction time is about 0.5 to 48 hours, preferably 0.5 to 24 hours.
• the salt represented by the formula (IV) can be obtained by filtering the precipitate.
• the form of the salt of the present invention is not particularly limited, and may be an oily substance, amorphous (amorphous), or crystalline.
• a preferred salt form is a crystal.
• Examples of the salt in the form of crystals include 2.0 hydrochloride, 2.5 hydrochloride, dihydrobromide, 2.5 odorous hydrochloride, 2 mesylate, 3 mesylate, 2 tosylate, 2-besylate, 2-naphthalene-1-sulfonate, 2-naphthalene-2-sulfonate, 2 (+)-camphorsulfonate, 2 maleate, 2 fumarate, or 2L-tartrate, etc. Can be illustrated. These salts can also be characterized by diffraction peaks in the powder X-ray diffraction pattern.
• the crystal polymorphs of 2.0 hydrobromide are referred to as Form A, Form B and Form C.
• the salt in the crystalline form is also referred to herein as 2.0 hydrobromide, where appropriate.
• the crystal polymorphs of 2-tosylate are A, B and C
• the crystals of 2-tosylate are A, B and C
• the crystals of 2-besylate are A.
• Forms B and B, 2 maleate crystal polymorphs are referred to as A and B forms
• 2 fumarate crystal polymorphs are referred to as A and B forms, respectively.
• the solvate of the salt of the present invention may exist as a solvate such as hemi, mono-, di-, tri-, tetra-, penta, hexa and the like.
• Solvents used for crystallization (alcohols (such as methanol, ethanol, or IPA), aldehydes, ketones (such as acetone), or esters (such as ethyl acetate)) and water contained in these solvents are contained in the crystal lattice. Can be incorporated. In general, it is impossible to predict the force at which a solvent will become a solvate or a non-solvate during crystallization and subsequent manufacturing steps. They depend on the compound, the production conditions and the combination of various interactions between the chosen solvent, especially water.
• the salt of the present invention may be a solvate of a solvent (such as water or an organic solvent) or a non-solvate. That is, the salt of the present invention may be a hydrate or a non-hydrate. May be. In the case of a hydrate, the amount of water to be hydrated may vary depending on various conditions, but is preferably a hydrate of 2.0 or less, more preferably 1.0 to 2.0 hydrate.
• the salt of the present invention may contain a solvent that is safe for mammals (such as those that are pharmaceutically, pharmacologically, or physiologically acceptable), or may be solvated with the solvent. May be.
• solvents are those whose daily intake allowance (“PDE”) exceeds 10 mg / day in the “ICH Guidelines for Residual Solvent Q3C” and / or classes in the “ICH Guidelines for Residual Solvent Q3C” The power of 3 is also chosen.
• ethanol 1-propanol, IPA, 1-butanol, 2-butanol, 1-pentanol, acetic acid, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate
• examples include formic acid, ethyl formate, acetone, methyl ethyl ketone, methyl isobutyl ketone, heptane, pentane, jetyl ether, t-butyl methyl ether, THF, anisole, tamen, and dimethyl sulfoxide.
• solvents ethanol is preferred.
• the content of “solvent” is 50000 ppm or less, preferably 5000 ppm or less.
• the salt of the present invention can be produced by a method known per se, for example, Compound I, hydrochloric acid, hydrobromic acid, nitric acid, mesylic acid, maleic acid, tosylic acid, besylic acid, naphthalene-1 -Sulfonic acid, naphthalene-2-sulphonic acid, gallic acid, (+) _ camphorsulphonic acid, (-)-camphorsulfonic acid, fumaric acid, sulfuric acid, succinic acid, L-tartaric acid, ethanedisulfonic acid, Chenic acid or phosphoric acid power
• the salt of the present invention can be obtained by reacting with a selected organic acid or inorganic acid.
• This reaction is generally performed in the absence of a solvent or in an inert solvent.
• inert solvents include water, alcohols (such as methanol, ethanol, 1-propanol, IPA, or butanol), ketones (such as acetone or methyl ethyl ketone), and nitriles (acetonitrile).
• amides (formamide, ⁇ , ⁇ -dimethylformamide, ⁇ , ⁇ -dimethylacetamide, or 1,3-dimethyl-2-imidazolidinone), ethers (jet ether, Diisopropyl ether, t-butyl methyl ether, 1,4-dioxane, or THF), esters (such as ethyl formate, ethyl acetate, or propyl acetate), halogenated hydrocarbons (dichloromethane, chloroform, Or 1,2-dichloroethane, etc.), carbonization Examples include hydrogens (such as n- hexane, cyclohexane, benzene, or toluene), sulfoxides (such as dimethyl sulfoxide), polar solvents (such as sulfolane or hexamethylphosphorylamide), or any mixed solvent thereof. It is done. Among these solvents,
• the "inert solvent” is generally used in an amount of 1 to 100 w / v%, preferably 2 to 50 w / v%, relative to Compound I.
• the reaction temperature is usually ⁇ 20 ° C. and the reflux temperature of the solvent, preferably 0 ° C. and the reflux temperature of the solvent.
• the reaction time is usually about 1 minute to 24 hours, preferably about 10 minutes to 6 hours, more preferably about 30 minutes to 3 hours.
• the salt thus obtained is isolated from the reaction mixture by a separation means known per se (concentration, concentration under reduced pressure, solvent extraction, crystallization, recrystallization, phase transfer, chromatography, etc.) It can be purified.
• the salt of Compound I can be obtained in the crystalline state.
• crystallization method include those known per se, such as crystallization from solution, crystallization from steam, and crystallization of melt strength (AS Myerson Ed., Handbook of Industrial, rystallization second Edition, Butterworth— Heinemann 200 2).
• Examples of the method for "crystallization of solution force" include a concentration method, a slow cooling method, a reaction method (diffusion method or electrolysis method), a hydrothermal growth method, a flux method, and the like.
• Examples of the solvent to be used include the same solvents as the “inert solvent”.
• Examples of the method of "vapor-powered crystal” include a vaporization method (a sealed tube method or a gas flow method), a gas phase reaction method, a chemical transport method, and the like.
• crystallization of the salt of Compound I crystallization by cooling of a solution in which the salt of Compound I is dissolved by heating to 40 ° C to the reflux temperature of the solvent used, or the salt of Compound I is used. Crystallization or the like by adding a poor solvent to a solution (particularly concentrated solution) in which is dissolved.
• an X-ray analysis method is generally used as a method for analyzing the obtained crystal. The measurement results of X-ray analysis show that the force 2 ⁇ value expressed as the diffraction intensity on the Y axis and the diffraction angle (2 ⁇ ) on the horizontal axis varies within a certain range even when the same crystal form is measured. Is observed.
• ⁇ 0.2 ° is a general variation, but a larger error may occur depending on the measurement conditions.
• those skilled in the art will compare crystal forms in consideration of these variations.
• the salt of the present invention or a solvate thereof may cause a slight shift in diffraction angle depending on the water content, and these are also included in the scope of the present invention.
• the salt of the present invention or a solvate thereof (hereinafter simply referred to as the salt of the present invention) has excellent stability, it can be stored at room temperature over a long period of time, and it is a complicated operation in the production process and storage. It is useful as a drug substance for pharmaceuticals because it is not necessary and it is easy to formulate. Furthermore, since the salt of the present invention has high solubility in water, a dosage form with a higher degree of freedom can be developed as an injectable preparation.
• the carrier of the present invention is pharmaceutically acceptable (excipient, binder, disintegrant, flavoring agent, flavoring agent, emulsifier, diluent, or solubilizer) and the like.
• Pharmaceutical compositions or formulations obtained by mixing (tablets, pills, capsules, granules, powders, syrups, emulsions, elixirs, suspensions, solutions, injections, drops, or sittings) In the form of an agent etc.) orally or parenterally.
• the pharmaceutical composition can be formulated according to a usual method.
• parenteral includes subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, infusion method, and the like.
• injectable preparations can be prepared by methods known in the art.
• Suppositories for rectal administration can be prepared by mixing the drug with an appropriate excipient.
• solid dosage forms for oral administration include those mentioned above such as powders, granules, tablets, pills, capsules and the like.
• liquid preparations for oral administration include pharmaceutically acceptable emulsions, syrups, elixirs, suspensions, and solutions.
• the dosage of the salt of the present invention is the age, body weight, general health condition, sex, meal, administration time, dosage. It will be determined by considering these and other factors depending on the method of administration, the rate of excretion, the combination of drugs, or the condition of the patient being treated at the time.
• the salt of the present invention can be used safely with low toxicity, and its daily dose varies depending on the patient's condition, body weight, type of salt, route of administration, etc.
• 0.05 to 50 mg / kg body weight / day is administered in one to several times a day.
• thermal analysis shows the temperature at the intersection (onset value) on the extension of the straight line part before melting and the straight line part during melting in the heat curve (onset value) and the temperature at the inflection point near the melting point ( peak top value).
• the powder X-ray diffraction pattern showed a characteristic peak at an angle of 2 ⁇ ( ⁇ 0.2 °) o-NMR was measured with a 300 MHz nuclear magnetic resonance spectrometer.
• the chemical shift of ' ⁇ - ⁇ MR was expressed in parts per million (ppm) using tetramethylsilane (TMS) as an internal standard and relative delta ( ⁇ ) values.
• Coupling constants indicate trivial multiplicity in hertz (Hz), expressed as s (singlet), d (doublet), t (triplet), m (multiplet), etc.
• Infrared spectroscopic (IR) absorbance intensities were expressed as st (strong), m (medium), and w (weak).
• Example 1 60 mg of the title compound of Example 1 was suspended in 3.0 mU of ethyl acetate and heated to reflux for 13 hours. After cooling at room temperature, the precipitate was collected by filtration and dried under hot air at 40 ° C. to give the title compound as crystals (50 mg yield 85%).
• This toluene layer was washed with 90 L of 5% aqueous sodium hydrogen carbonate solution and 90 L of water in this order, and concentrated to dryness under reduced pressure.
• 224 L of IPA was added, and 25.08 kg of 48% hydrobromic acid was added dropwise at about 80 ° C., followed by refluxing for 2.5 hours.
• the reaction was cooled and stirred at about 60 ° C for 1.5 hours, then at about 40 ° C for 2 hours, and further at room temperature for 2 hours.
• the precipitate was collected by filtration, washed with IPA 30 L, and dried under warm air to give the title compound solid (29.76 kg, yield 91%).
• Test example 1 [0065] Measurement of powder X-ray diffraction
• FIG. 2 shows the result of the powder X-ray diffraction measurement of the A-form crystal of the title compound of Example 5.
• FIG. 3 shows the result of the powder X-ray diffraction measurement of the B-form crystal of the title compound of Example 5.
• FIG. 4 shows the results of powder X-ray diffraction measurement of the C-form crystal of the title compound of Example 5.
• Test example 2 shows the results of the powder X-ray diffraction measurement of the A-form crystal of the title compound of Example 5.
• FIG. 3 shows the result of the powder X-ray diffraction measurement of the B-form crystal of the title compound of Example 5.
• FIG. 4 shows the results of powder X-ray diffraction measurement of the C-form crystal of the title compound of Example 5.
• the moisture absorption property of the title compound of Example 3 was measured using a moisture adsorption measuring device under the following measurement conditions.
• a visual method was used which can easily grasp the maximum solubility with a small amount of sample.
• the temperature was measured at 37 ° C.
• About 3 mg of the title compound of Example 3 was placed in a sample bottle with a screw cap, and 0.15 mL of the test solution was collected and sealed. After the sample was dispersed by applying ultrasonic waves for 1 minute, this was added together and placed in a constant-temperature shaking water bath stabilized at 37 ° C. After shaking for 1 hour, dissolution was confirmed by visual observation.
• the solubility of the title compound of Example 3 in water was 20 mg / mL or more at 37 ° C.
• the salt of Compound I or its solvate, or each new crystalline polymorph has improved stability, improved hygroscopicity (deliquescent), rapid isolation from solvents, and ease of formulation. Promote the development of Compound I as a pharmaceutical product with one or more selected properties [0070] This application was filed with priority from Japanese Patent Application No. 2005-04-1851.

Landscapes

• Organic Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Diabetes (AREA)
• General Health & Medical Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Engineering & Computer Science (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• General Chemical & Material Sciences (AREA)
• Emergency Medicine (AREA)
• Endocrinology (AREA)
• Hematology (AREA)
• Obesity (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Medicinal Preparation (AREA)
• Peptides Or Proteins (AREA)
• Pyrrole Compounds (AREA)

Priority Applications (13)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=36916526

Family Applications (1)

Country Status (14)

Cited By (27)

Families Citing this family (17)

Citations (1)

Family Cites Families (19)

• 2006
  • 2006-02-17 CN CN2011103035812A patent/CN102372705A/zh active Pending
  • 2006-02-17 CN CN201110303552.6A patent/CN102372704B/zh active Active
  • 2006-02-17 WO PCT/JP2006/302827 patent/WO2006088129A1/ja active Application Filing
  • 2006-02-17 EA EA200701756A patent/EA013119B1/ru not_active IP Right Cessation
  • 2006-02-17 US US11/816,493 patent/US8003790B2/en not_active Expired - Fee Related
  • 2006-02-17 EP EP13157384.2A patent/EP2602259A3/en not_active Withdrawn
  • 2006-02-17 CN CN2006800048659A patent/CN101119991B/zh not_active Ceased
  • 2006-02-17 CA CA2598301A patent/CA2598301C/en not_active Expired - Fee Related
  • 2006-02-17 KR KR1020137016412A patent/KR20130076903A/ko not_active Application Discontinuation
  • 2006-02-17 AU AU2006215041A patent/AU2006215041B2/en not_active Ceased
  • 2006-02-17 KR KR1020077021144A patent/KR101352650B1/ko active IP Right Review Request
  • 2006-02-17 NZ NZ561489A patent/NZ561489A/en not_active IP Right Cessation
  • 2006-02-17 JP JP2007503744A patent/JP4208938B2/ja active Active
  • 2006-02-17 EP EP06713968.3A patent/EP1854795B1/en not_active Not-in-force
  • 2006-02-17 ES ES06713968.3T patent/ES2588164T3/es active Active
  • 2006-02-17 BR BRPI0607863A patent/BRPI0607863B8/pt not_active IP Right Cessation
  • 2006-02-17 TW TW095105368A patent/TWI403511B/zh not_active IP Right Cessation
  • 2006-02-17 MX MX2007010054A patent/MX2007010054A/es active IP Right Grant
• 2008
  • 2008-04-30 JP JP2008119236A patent/JP2008214358A/ja active Pending
• 2011
  • 2011-07-29 US US13/194,501 patent/US8604198B2/en not_active Expired - Fee Related
• 2012
  • 2012-10-10 JP JP2012224923A patent/JP2013032376A/ja active Pending

Patent Citations (1)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events